Show simple item record

dc.contributor.authorLyon, Malcolm
dc.contributor.authorDeakin, Jon A
dc.contributor.authorRahmoune, H
dc.contributor.authorFernig, D G
dc.contributor.authorNakamura, T
dc.contributor.authorGallagher, John T
dc.date.accessioned2010-02-24T13:54:42Z
dc.date.available2010-02-24T13:54:42Z
dc.date.issued1998-01-02
dc.identifier.citationHepatocyte growth factor/scatter factor binds with high affinity to dermatan sulfate. 1998, 273 (1):271-8 J. Biol. Chem.en
dc.identifier.issn0021-9258
dc.identifier.pmid9417075
dc.identifier.urihttp://hdl.handle.net/10541/92922
dc.description.abstractWe have demonstrated by affinity chromatography that hepatocyte growth factor/scatter factor (HGF/SF) binds strongly to dermatan sulfate (DS), with a similar ionic strength dependence to that previously seen with heparan sulfate (HS). Analysis of binding kinetics on a biosensor yields an equilibrium dissociation constant, KD, of 19.7 nM. This corresponds to a 10-100-fold weaker interaction than that with HS, primarily due to a faster dissociation rate of the complex. The smallest DS oligosaccharide with significant affinity for HGF/SF by affinity chromatography appears to be an octasaccharide. A sequence comprising unsulfated iduronate residues in combination with 4-O-sulfated N-acetylgalactosamine is sufficient for high affinity binding. The presence of 2-O-sulfation on the iduronate residues does not appear to be inhibitory. These observations concur with our previous suggestions, from analyses of HS binding (Lyon, M., Deakin, J. A., Mizuno, K., Nakamura, T., and Gallagher, J.T. (1994) J. Biol. Chem. 269, 11216-11223), that N-sulfation of hexosamines and 2-O-sulfation of iduronates are not absolute requirements for glycosaminoglycan binding to HGF/SF. This is the first described example of a high affinity interaction between a growth factor and DS, and is likely to have significant implications for the biological activity of this paracrine-acting factor.
dc.language.isoenen
dc.subject.mesh3T3 Cells
dc.subject.meshAnimals
dc.subject.meshBinding, Competitive
dc.subject.meshCarbohydrate Conformation
dc.subject.meshCell Line
dc.subject.meshDermatan Sulfate
dc.subject.meshDogs
dc.subject.meshHepatocyte Growth Factor
dc.subject.meshHumans
dc.subject.meshKinetics
dc.subject.meshMice
dc.subject.meshMice, Inbred BALB C
dc.subject.meshOligosaccharides
dc.subject.meshProtein Binding
dc.titleHepatocyte growth factor/scatter factor binds with high affinity to dermatan sulfate.en
dc.typeArticleen
dc.contributor.departmentCancer Research Campaign & University of Manchester, Department of Medical Oncology, Christie Hospital National Health Service Trust, Manchester M20 4BX, United Kingdom. MLyon@picr.man.ac.uken
dc.identifier.journalThe Journal of biological chemistryen
html.description.abstractWe have demonstrated by affinity chromatography that hepatocyte growth factor/scatter factor (HGF/SF) binds strongly to dermatan sulfate (DS), with a similar ionic strength dependence to that previously seen with heparan sulfate (HS). Analysis of binding kinetics on a biosensor yields an equilibrium dissociation constant, KD, of 19.7 nM. This corresponds to a 10-100-fold weaker interaction than that with HS, primarily due to a faster dissociation rate of the complex. The smallest DS oligosaccharide with significant affinity for HGF/SF by affinity chromatography appears to be an octasaccharide. A sequence comprising unsulfated iduronate residues in combination with 4-O-sulfated N-acetylgalactosamine is sufficient for high affinity binding. The presence of 2-O-sulfation on the iduronate residues does not appear to be inhibitory. These observations concur with our previous suggestions, from analyses of HS binding (Lyon, M., Deakin, J. A., Mizuno, K., Nakamura, T., and Gallagher, J.T. (1994) J. Biol. Chem. 269, 11216-11223), that N-sulfation of hexosamines and 2-O-sulfation of iduronates are not absolute requirements for glycosaminoglycan binding to HGF/SF. This is the first described example of a high affinity interaction between a growth factor and DS, and is likely to have significant implications for the biological activity of this paracrine-acting factor.


This item appears in the following Collection(s)

Show simple item record